Abstract A027: Clonal hematopoiesis of indeterminate potential (CHIP) in patients with advanced NSCLC treated with immune checkpoint blockers (ICB) as monotherapy: Analysis of the PREMIS study. [R]
Authors: Julieta Elena Rodriguez, Capucine Baldini, Francois Xavier Danlos, Aurelien Marabelle, Maxime Frelaut, Marco Tagliamento, Mihaela Aldea, Benjamin Besse, Jean Baptiste Micol, Christophe Marzac, Nathalie Chaput, Christophe Massard
Journal: Cancer Research (2023)

Abstract Introduction: Immunotherapy is one of the mainstays of lung cancer treatment. The results presented in pivotal trials do not always reflect real life, since patients (pts) are more selected for prognostic factors. Cancer is associated with advanced age and aging is the main risk factor for developing CHIP, which refers to the finding of one or more mutations affecting genes involved in hematologic malignancies in pts without hematologic disease per se. Objective: To evaluate CHIP prevalence in a prospective cohort of 104 pts treated with ICB for NSCLC and to correlate CHIP and clinical outcomes. Materials and methods: We performed a Next-Generation Sequencing (NGS) with a panel of 74-genes dedicated to hematological alteration on DNA extracted from whole blood collected before the first administration of an ICB, within the PREMIS trial (NCT03984318). To estimate the prevalence of CHIP, we selected the following 4 CHIP genes; DNMT3A, TET2, ASXL1 and JAK2. CHIP prevalence was assessed according to two variant allele frequency (VAF) thresholds (1% and 2%). The results were analyzed for the entire population and for the subgroup of pts older than 70 years. Results: We included 104 pts; 68 pts (65%) male, median age of 68 years [range 31-87] and adenocarcinoma represented the 68%. PD-L1 &amp;lt;50%: 28% and &amp;gt;50%: 43%. ICB setting was 1°L 41%; 2°L 47%; &amp;gt; 3°L 11%, and the most used ICB was Pembrolizumab in 63% of pts. Among the 88% of the pts who discontinued treatment, 63% did it due to disease progression and 13% due to toxicity (pneumonitis was the most frequent adverse event in pts with CHIP). Overall, at least 1 CHIP mutation was found in 35 pts (34%). Incidence at VAF 1% and 2% for each mutation were DNMT3A 80% and 69%, TET2 11% respectively, ASXL1 11% respectively and JAK2 6% and 3%; for older pts subgroup VAF at 1% and 2% were: DNMT3A 71% and 59% and for TET2 and ASXL1 24% respectively for each mutation. Only 4% of pts had more than 1 CHIP mutation. No pts developed hematological disease during the follow up. There was no difference in CHIP prevalence according to line of treatment. CHIP pts achieved disease control in 51%. PFS and OS results will be presented at the conference. Conclusion: CHIP is commonly found in pts with solid tumors, including NSCLC, with a prevalence in our cohort of 34%, which is lower than that reported in literature. No pts developed a characterized hematological disease during follow up. Survival outcomes will be presented at the conference. Citation Format: Julieta Elena Rodriguez, Capucine Baldini, Francois Xavier Danlos, Aurelien Marabelle, Maxime Frelaut, Marco Tagliamento, Mihaela Aldea, Benjamin Besse, Jean Baptiste Micol, Christophe Marzac, Nathalie Chaput, Christophe Massard. Clonal hematopoiesis of indeterminate potential (CHIP) in patients with advanced NSCLC treated with immune checkpoint blockers (ICB) as monotherapy: Analysis of the PREMIS study. [R] [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr A027.